Document Type
Article
Publication Date
3-14-2019
Identifier
DOI: 10.1038/s41467-019-09184-z; PMCID: PMC6418220
Abstract
Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.
Journal Title
Nat Commun
Volume
10
Issue
1
First Page
1209
Last Page
1209
MeSH Keywords
Adipose Tissue; Adult; Aged; Cardiovascular Diseases; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Gene Expression Profiling; Genome, Human; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Lipids; Male; Metabolic Diseases; Middle Aged; Polymorphism, Single Nucleotide; Regulatory Sequences, Nucleic Acid; Sequence Analysis, DNA
Keywords
Adipose Tissue; Adult; Aged; Cardiovascular Diseases; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Gene Expression Profiling; Genome, Human; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Lipids; Male; Metabolic Diseases; Middle Aged; Polymorphism, Single Nucleotide; Regulatory Sequences, Nucleic Acid; Sequence Analysis, DNA
Recommended Citation
Allum F, Hedman ÅK, Shao X, et al. Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements. Nat Commun. 2019;10(1):1209. Published 2019 Mar 14. doi:10.1038/s41467-019-09184-z
Comments
Grant support
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Publisher's Link: https://doi.org/10.1038/s41467-019-09184-z